Cancer trails only cardiovascular disease as the leading cause of mortality in the US. Cancers of the lung,[unreadable] colon, breast and prostate, all derived from epithelium, account for the majority of cancer-related deaths.[unreadable] Recently, our group has made two important discoveries about the various populations of normal and cancer[unreadable] cells in tumors. First, we find that in tumors arising in the breast, colon and head and neck only a subset of[unreadable] the cancer cells, called cancer stem cells, drive the growth and spread of the tumor and are ultimately[unreadable] responsible for patient morbidity and mortality. Next, compared to normal tissue fibroblasts, tumor stroma[unreadable] fibroblasts are "activated" and make high levels of growth factors implicated in carcinogenesis. The goal of[unreadable] this proposal which is to understand the mechanisms by which colon cancer stem cells interact with the[unreadable] tumor stroma, addresses the central theme of this RFA. As envisioned by the RFA, the investigators are a[unreadable] highly collaborative, multi-disciplinary group drawn from several departments and schools of Stanford[unreadable] University including members from the Departments of Bioengineering, Biochemistry, Statistics, Health[unreadable] Research Policy, Surgery, Medicine and the Stanford Institute of Stem Cell Biology. The team is developing[unreadable] novel, cutting edge technology to understand at the molecular and cellular level how the cancer stem cells[unreadable] interact with the tumor stroma. The grant consists of 2 highly interactive projects as well as an administrative[unreadable] core and a bioinformatics core. Project 1 will obtain gene expression profiles from tumor components[unreadable] including cancer stem cells and normal stromal cells. The gene expression data will be used to identify[unreadable] stromal factors that drive cancer stem cell growth in novel high throughput assays. Project 2 has two parts.[unreadable] We will use microfluidic devices to do single cell gene expression arrays to determine whether there is[unreadable] cellular heterogeneity of the markers described in Project 1 to enrich cancer stem cells. If so, each cell[unreadable] population will be analyzed in Project 1 to determine whether we can further enrich cancer stem cells. The[unreadable] second part will use microfluidic devices to identify stromal cell factors that drive proliferation of colon cancer[unreadable] stem cells. Any factors identified in Project 2 that drive proliferation of the cancer stem cells will be tested in[unreadable] Project 1 to see if the factors cause expansion of cancer stem cells or if they drive them to differentiate into[unreadable] cancer cells that no longer can form a tumor. [unreadable] [unreadable] [unreadable]